Presented by: Michael Frumer MD
Rabin Medical Center

Introduction

Recently, the added-value of Lutetium-177-PSMA (LuPSMA) was demonstrated in metastatic castration-resistant prostate cancer patients. A decrease in PSA was observed among 70% of the patients who were treated with LuPSMA in addition to standard hormonal treatment. However, the dynamics of prostate specific antigen (PSA) in response to LuPSMA-only treatment in localized high risk prostate cancer (HRPCa) has not been described in the literature.

Materials

We analyzed data from a phase I neoadjuvant LuPSMA trial of HRPCa patients who underwent radical prostatectomy (RP). Each patient received 2 or 3 LuPSMA, two weeks apart at a dose of 7.4 Gbq per treatment until one month before RP. Serum PSA level was measured before and after each LuPSMA dose. We described PSA response to treatment and compared the clinical and histological characteristics between patients with > or < 50% decrease in PSA.

Results

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14 patients with a median baseline PSA value of 11.8 ng/dL (IQR 9, 17) were included, of which 6 patients were treated with two doses of lutetium and 8 patients with three doses.

A decrease in PSA of at least 0.3 ng/dl was observed in 57% of patients after the first lutetium dose and in 93% of patients after the second lutetium. The median percentage of change after the second dose was -17% (IQR -9, -50). After the third dose, 100% of patients showed a decrease in PSA and the median percentage of change was -34% (IQR -11, -60).

PSA decreased in >50% and <50% in 4 (30%) and 10 (30%) patients, respectively. There were no differences in the baseline median PSA between these subgroups (9.5 and 12.7 ng/dL, respectively (p>0.05)).

At final surgical histology down-grading was observed in 3 of 4 patients with >50% PSA decrease and in none of the patients with <50% decrease (P=0.02). No differences were found between the subgroups in terms of demographic characteristics, clinical staging or the biochemical response after surgery.

Conclusion

This study shows that neadjuvant LuPSMA in localized HRPCa is associated with a dose-dependent decrease in PSA that can reach 34% after 3 LuPSMA doses. Although a decrease of >50% in PSA predicted down-grading on RP final histology, the long term implications are not clear.

Funding

Dr. Adolph and Klara Brettler Endowment Fund in Urology, Sackler Faculty of Medicine, and Tel Aviv University.

Co-Authors

Daniel Kedar, MD
Rabin Medical Center

Jack Baniel, MD
Rabin Medical Center

David Groshar, MD
Rabin Medical Center

Hanna Bernstine, MD
Rabin Medical Center

Maxim Yakimov, MD
Rabin Medical Center

Eli Rosenbaum, MD
Rabin Medical Center

Shay Golan, MD
Rabin Medical Center